Effect of angiotensin II on diabetic glomerular hyperpermeability: an in vivo permeability study in rats.

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg-1·min-1 for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ∼20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10-90 Å (Ficoll70-90 Å), were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (θ for Ficoll70-90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll70-90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.

Patterns of urinary albumin and IgM associate with markers of vascular ageing in young to middle-aged individuals in the Malmö offspring study.

BACKGROUND: Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study was to investigate the association between urinary IgM, albuminuria, and vascular parameters reflecting arterial structure and function. METHODS: Subjects of the present study were from the Malmö Offspring study (MOS) cohort, and included 1531 offspring (children and grand-children) to first-generation subjects that participated in the Malmö Diet Cancer-Cardiovascular Arm study cohort. At baseline, technical measurements of arterial stiffness (carotid-femoral pulse wave velocity; c-f PWV), carotid arterial morphology, 24-h ambulatory blood pressure recordings, ankle-brachial-index (ABI), and evaluation of endothelial function (reactive hyperemia index, RHI) were performed. Urinary (U) IgM, U-albumin, and U-creatinine were measured. Multivariate adjusted logistic regression was used to test whether U-IgM excretion and increasing urinary albumin excretion were related to vascular parameters. RESULTS: Detectable U-IgM was independently associated with higher systolic blood pressure, odds ratio (OR) 1.021, 95% confidence interval (CI, 1.003-1.039), p = 0.025 and lower ABI; ABI dx: OR 0.026, 95% CI (0.002-0.381), p = 0.008, ABI sin: OR 0.040, 95% CI (0.003-0.496), p = 0.012. Low-grade albuminuria was independently associated with systolic and diastolic blood pressure, aortic blood pressure, the c-f PWV and the number of carotid intima plaques (p < 0.05). CONCLUSIONS: In young to middle-aged, mostly healthy individuals, increased U-IgM excretion and low-grade albuminuria are associated with adverse vascular parameters. Increased U-IgM excretion may reflect subclinical peripheral atherosclerosis, whereas increased U-albumin excretion is associated with a wide range of cardiovascular abnormalities. This may reflect different pathophysiological mechanisms.

KIN AND NON-KIN MARRIAGES AND FAMILY STRUCTURE IN A RICH TRIBAL SOCIETY.

Human consanguinity is often attributed to poverty, lack of education and social insecurity. Nevertheless, kin unions continue to be arranged in socioeconomically transformed societies. This study examined the structure of families and marriages in the rich tribal society of the United Arab Emirates, which has had a high gross domestic product for the last two generations and currently has one of the highest in the world. The respondents were 217 national medical students whose families are proportionally distributed to the population of the country emirates. The rate of parental consanguinity (defined as a union of any two cousins) was 36%. The social status and mean size of consanguineous and non-consanguineous families were not significantly different. In non-consanguineous families, polygamy was more common and the number of half-siblings per family was higher. The extended families were on average 7% larger among non-consanguineous families. In contrast, for the extended families of the participants' grandparents, non-consanguineous families were smaller than their consanguineous counterparts. Participants from consanguineous families indicated that marriage of either a son or daughter was more difficult to arrange than did participants from non-consanguineous families. Though consanguineous parents had their offspring marry consanguineously more often than non-consanguineous parents, the numbers of married offspring in the two groups of families were not different. Consanguineous parents have more difficulty than non-consanguineous parents in finding spouses for themselves and for their offspring, and they arranged kin marriages for their children more often.

Plasma pro-inflammatory cytokines, IgM-uria and cardiovascular events in patients with chest pain: A comparative study.

BACKGROUND: Risk stratification of patients presenting with acute chest pain is crucial for immediate and long-term management. Traditional predictors are suboptimal; therefore inflammatory biomarkers are studied for clinical assessment of patients at risk. Recently, we reported the association of IgM-uria with worse cardiovascular outcome in patients with acute chest pain. In this study, in the same cohort of patients with chest pain, we compared the value of IgM-uria to pro-inflammatory cytokines in predicting the occurrence of subsequent cardiovascular events. METHODS: A total of 178 consecutive patients presenting with acute chest pain to the emergency department at the University Hospital of Lund, were recruited. Twenty-seven of 57 patients with acute coronary syndrome (ACS), and 18 of 118 patients with non-specific chest pain at baseline developed a subsequent major cardiovascular event during the 18 months follow-up. Urinary proteins (IgM-uria and Microalbuminuria) and plasma inflammatory markers (IL-6, Il-8, IL-10, IFN-γ and TNF-α) were measured at time of admission. RESULTS: Using the receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.71 (95%CI 0.61-0.81) for IgM-uria, 0.61 (95%CI 0.51-0.71) for IL-6, 0.63 (95%CI 0.53-0.72) for IL-8, 0.65 (95%CI 0.56-0.74) for IL-10, and 0.64 (95% CI 0.54-0.74) for TNF-α. In multivariate Cox-regression analysis adjusted for age, microalbuminuria, IgM-uria, IL-10, TNF-α, troponin T, hsCRP and ACS at baseline; IgM-uria was the only biomarker that remained an independent predictor of outcome (HR = 4.2, 95%CI 2.2-7.8, p < 0.001). CONCLUSION: In patients with chest pain with or without acute coronary syndrome, IgM-uria could better predict the occurrence of cardiovascular events than plasma pro-inflammatory cytokines.

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness.

BACKGROUND: Treatment of idiopathic membranous nephropathy with nephrotic syndrome is still controversial. There is currently little known about the clinical use of renal biomarkers which may explain contradictory results obtained from clinical trials. In order to assess whether IgG-uria can predict the outcome in membranous nephropathy, we examined the value of baseline EF-IgG in predicting remission and progression of nephrotic syndrome. METHODS: In a prospective cohort of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic syndrome we validated the ability of the clinically available urine biomarker, IgG, to predict the risk of kidney disease progression and the beneficial effect of immunosuppression with steroids and cyclophosphamide. The fractional excretion of IgG (FE-IgG) and α1-microglobulin (FE-α1m), urine albumin/creatinine ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was progression to end stage kidney failure or kidney function (eGFR) decline ≥ 50% of baseline. Patients were followed up for 7.2 ± 4.1 years (range 1-16.8). RESULTS: High FE-IgG (≥ 0.02) predicted an increased risk of kidney failure (Hazard Ratio, (HR) 8.2, 95%CI 1.0-66.3, p=0.048) and lower chance of remission (HR 0.18, 95%CI 0.09-0.38, p<0.001). The ten-year cumulative risk of kidney failure was 51.7% for patients with high FE-IgG compared to only 6.2% for patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG entered remission compared to 90% of patients with low FE-IgG. Combined treatment with steroids and cyclophosphamide decreased the progression rate (-40%) and increased the remission rate (+36%) only in patients with high FE-IgG. CONCLUSION: In idiopathic membranous nephropathy patients with nephrotic syndrome, FE-IgG could be useful for predicting kidney disease progression, remission, and response to treatment.

Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease.

BACKGROUND: Changes in glycosylation of serum proteins are common, and various glycoforms are being explored as biomarkers in cancer and inflammation. We recently showed that glycoforms detected by endogenous galectins not only provide potential biomarkers, but also have different functions when they encounter galectins in tissue cells. Now we have explored the use of a combination of two galectins with different specificities, to further increase biomarker sensitivity and specificity. METHODS: Sera from 14 women with metastatic breast cancer, 12 healthy controls, 14 patients with IgA-nephritis (IgAN), and 12 patients with other glomerulonephritis were fractionated by affinity chromatography on immobilized human galectin-1 or galectin-8N, and the protein amounts of the bound and unbound fractions for each galectin were determined. RESULTS: Each galectin bound largely different fractions of the serum glycoproteins, including different glycoforms of haptoglobin. In the cancer sera, the level of galectin-1 bound glycoproteins was higher and galectin-8N bound glycoproteins lower compared to the other patients groups, whereas in IgAN sera the level of galectin-8N bound glycoproteins were higher. CONCLUSION: The ratio of galectin-1 bound/galectin-8N bound glycoproteins showed high discriminatory power between cancer patients and healthy, with AUC of 0.98 in ROC analysis, and thus provides an interesting novel cancer biomarker candidate. GENERAL SIGNIFICANCE: The galectin-binding ability of a glycoprotein is not only a promising biomarker candidate but may also have a specific function when the glycoprotein encounters the galectin in tissue cells, and thus be related to the pathophysiological state of the patient. This article is part of a Special Issue entitled Glycoproteomics.

Increased urinary IgM excretion in patients with chest pain due to coronary artery disease.

BACKGROUND: Micro-albuminuria is a recognized predictor of cardiovascular morbidity and mortality in patients with coronary artery disease. We have previously reported, in diabetic and non-diabetic patients, that an increased urinary excretion of IgM is associated with higher cardiovascular mortality. The purpose of this study was to investigate the pattern of urinary IgM excretion in patients with acute coronary syndrome (ACS) and its correlation to cardiovascular outcome. METHODS: Urine albumin, and IgM to creatinine concentration ratios were determined in 178 consecutive patients presenting with chest pain to the Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty eight (23 female) patients had ACS, 55 (19 female) patients had stable angina (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS). RESULTS: Urine albumin and IgM excretions were significantly higher in patients with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS-chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1 female) patients died of cardiovascular cause. A high degree of albuminuria and IgM-uria significantly predicted cardiovascular mortality and morbidity (HR = 2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (≥3 mg/mmol) with high IgM-uria (≥0.005 mg/mmol) had a 3-fold higher risk for cardiovascular new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p = 0.001). CONCLUSION: In patients with chest pain, an increased urine IgM excretion, is associated with coronary artery disease and long-term cardiovascular complications. Measuring urine IgM concentration could have a clinical value in risk stratification of patients with ACS.

Deficient editorial practices, perceived quality, and expedient scholarly publishing in a developing nation.

Background: There is increasing concern about the quality, integrity, and accessibility to research published in the developing world. This study explores the editorial practices and editors' perspectives to gain insight into the standard of scholarly publishing in Libya. Methods: Between 21 st January and 12 th February, 2022, the editors-in-chief (EC) of Libyan academic journals were invited to complete a questionnaire on editorial practices, degree of satisfaction with submitted and published manuscripts, review processes, and journal performance, as well as challenges facing the journals. Journal websites were examined for quality, and indexation coverage and citations were assessed. We examined the number of citations in Google Scholar for all 2019 articles published in each journal. Descriptive statistics were used to quantitatively summarize the data and thematic analysis was used for the narrative text. Results: 48 EC completed the questionnaire. The EC was affiliated with the institution that owns the journal in 92% of cases. Most EC (83%) were satisfied with the peer-review quality, 69% believed that most of their published papers add new ideas or findings, and 96% were satisfied with their journal's performance. However, despite the high degree of satisfaction, only one journal was indexed in Web of Science or Scopus and only 17% of the journals were indexed in Google Scholar. A qualitative assessment of journal websites revealed shortcomings in publishing practices in a large proportion of the journals. Conclusions: The discordance between the satisfaction of the journal editors and the journal quality indicators points to a break in the quality system of Libyan academic publishing. Similar expedient publishing practices might exist in other countries as well. A comprehensive action plan led by academic institutions to enforce high standards for scholarly publishing is needed to advance research and high-quality scholarly publications in developing countries.

Optimized serum ferritin prediction of iron overload in transfusion-dependent thalassemia: likelihood ratio and age-adjustment approach.

BACKGROUND: Early detection of iron overload in transfusion-dependent thalassemia (TDT) patients is critical to prevent complications and improve survival. OBJECTIVES: Evaluate the utility of serum ferritin (SF) in the prediction of hepatic and myocardial iron overload (HIO and MIO) compared to T2*-MRI. DESIGN: Retrospective SETTINGS: Governmental hospitals. PATIENTS AND METHODS: Patients with TDT who had T2*-MRI examinations between January 2016 to October 2019 were included. The predictive value of SF for detection of HIO and MIO was assessed by measuring area under the curve (AUC). A sample size of 123 cases was calculated to detect a correlation of 0.25 with 90% power and a two-sided type I error of 0.05. MAIN OUTCOME MEASURES: The correlation between SF and estimated hepatic iron concentration. SAMPLE SIZE: 137 TDT patients who required regular blood transfusions. RESULTS: The predictive value of SF was excellent for detection of HIO (AUC=0.83-0.87) but fair for detection of MIO (AUC=0.67). The two independent predictors of MIO were age and SF. The log of (age × SF) enhanced the SF predictive value for MIO (AUC=0.78). SF values of 700 and 1250 mg/L effectively excluded mild and moderate HIO with a sensitivity of 97.8% and 94.2%, respectively (LR-=0.1). While SF values of 1640 and 2150 mg/L accurately diagnosed mild and moderate HIO with a specificity of 95.55% and 96.4%, respectively (LR+>10). A log of (age × SF) cut-off value of 4.15 effectively excluded MIO (LR-=0.1), while a value of 4.65 moderately confirmed MIO (LR+=3.2). CONCLUSIONS: SF is an excellent predictor of hepatic IO in TDT. Age adjustment enhanced its myocardial IO predictive accuracy. Likelihood ratio-based SF cut-off values may help clinicians in risk stratification and treatment decision-making. LIMITATIONS: The laboratory data were gathered retrospectively and although the risk of selection bias for T2*-MRI examination is thought to be low, it cannot be ignored. CONFLICT OF INTEREST: None.

Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.

BACKGROUND: Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAcα2-3Gal). PURPOSE: The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of ß-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. METHODS: Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. RESULTS: Analysis of ~100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to ~100 controls, consistent with the known loss of galactosylation. A subgroup of ~15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA <0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. CONCLUSION: This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.

Score Gains on the NBME Subject Examinations in Internal Medicine Among Clerkship Students: a Two-Year Longitudinal Study from the United Arab Emirates.

Background: The impact of clinical proficiency on individual student scores on the National Board of Medical Examiners (NBME) Subject Examinations remains uncertain. We hypothesised that increasing the length of time spent in a clinical environment would augment students' performance. Methods: Performance on the NBME Subject Examination in Internal Medicine (NBME-IM) of three student cohorts was observed longitudinally. Scores at the end of two unique internal medicine clerkships held at the third and fourth years were compared. The score differences between the two administrations were compared using paired t-tests, and the effect size was measured using Cohen's d. Moreover, linear regression was used to assess the correlation between the NBME-IM score gains and performance on a pre-clinical Comprehensive Basic Science Examination (CBSE). A two-tailed p-value <0.05 was considered significant. Results: Of the 236 students enrolled during the third year, age, gender, CBSE, and NBME-IM scores were similar across all cohorts. The normalised score gain on the NBME-IM at the fourth year was 9.5% (range -38 to +45%) with a Cohen's d of 0.47. However, a larger effect size with a Cohen's d value of 0.96 was observed among poorly scoring students. Performance on the CBSE was a significant predictor of score gain on the NBME-IM (R 0.51, R 2 0.26, p-value < 0.001). Conclusions: Despite the increased length of clinical exposure, modest improvement in students' performance on repeated NBME-IM examination was observed. Medical educators need to reconsider how the NBME-IM is used in clerkship assessments.

Predicting Severe Disease and Critical Illness on Initial Diagnosis of COVID-19: Simple Triage Tools.

RATIONALE: This study was conducted to develop, validate, and compare prediction models for severe disease and critical illness among symptomatic patients with confirmed COVID-19. METHODS: For development cohort, 433 symptomatic patients diagnosed with COVID-19 between April 15th 2020 and June 30th, 2020 presented to Tawam Public Hospital, Abu Dhabi, United Arab Emirates were included in this study. Our cohort included both severe and non-severe patients as all cases were admitted for purpose of isolation as per hospital policy. We examined 19 potential predictors of severe disease and critical illness that were recorded at the time of initial assessment. Univariate and multivariate logistic regression analyses were used to construct predictive models. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration and goodness of fit of the models were assessed. A cohort of 213 patients assessed at another public hospital in the country during the same period was used to validate the models. RESULTS: One hundred and eighty-six patients were classified as severe while the remaining 247 were categorized as non-severe. For prediction of progression to severe disease, the three independent predictive factors were age, serum lactate dehydrogenase (LDH) and serum albumin (ALA model). For progression to critical illness, the four independent predictive factors were age, serum LDH, kidney function (eGFR), and serum albumin (ALKA model). The AUC for the ALA and ALKA models were 0.88 (95% CI, 0.86-0.89) and 0.85 (95% CI, 0.83-0.86), respectively. Calibration of the two models showed good fit and the validation cohort showed excellent discrimination, with an AUC of 0.91 (95% CI, 0.83-0.99) for the ALA model and 0.89 (95% CI, 0.80-0.99) for the ALKA model. A free web-based risk calculator was developed. CONCLUSIONS: The ALA and ALKA predictive models were developed and validated based on simple, readily available clinical and laboratory tests assessed at presentation. These models may help frontline clinicians to triage patients for admission or discharge, as well as for early identification of patients at risk of developing critical illness.

High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009).

BACKGROUND: There is a geographical variation in the incidence of childhood type 1 diabetes mellitus (T1DM) with a steady increase reported from some countries. However, data on the incidence of childhood T1DM in Kingdom of Saudi Arabia are limited. OBJECTIVE: To identify the incidence rate (IR) and epidemiological trends of childhood T1DM in the largest city of northwest Saudi Arabia. METHODS: All patients with newly diagnosed T1DM aged 0-12 yr living in the city between 2004 and 2009 were identified from different sources. The data were analyzed according to age, sex, and month of presentation. RESULTS: In total, 419 patients (249 girls) were diagnosed between 2004 and 2009 inclusive. The mean age at diagnosis was 6.9 ± 3.5 yr. The mean annual age-standardized IR was 29.0 (95% confidence interval 26.0-32.0). The incidence was significantly higher in the 10-12-yr age group than in younger children (p < 0.001) and higher in girls than in boys (33.0 vs. 22.2 per 100 000; p < 0.001). There was no significant increase in the annual incidence during the 6-yr period (p = 0.68) and more cases were diagnosed during autumn and winter months (p = 0.002). CONCLUSIONS: Al-Madinah city has the highest reported incidence of childhood T1DM in the Middle East and North Africa region. Further studies to identify the reasons for this high incidence are needed.

The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study.

BACKGROUND: Proteinuria is the hallmark of glomerular disease and non-selective proteinuria is often associated with progression to renal failure. The predictive value of urine IgG excretion was studied comprehensively in patients with nephrotic syndrome. In the present follow-up study, we examine the predictive value of IgG-uria in patients with idiopathic glomerular diseases with a wide range of proteinuia. METHODS: A total of 189 (113 males and 76 females) patients with idiopathic glomerulonephritis and serum creatinine of less than 150 µmol/L diagnosed between 1993 and 2004 were followed up to their last visit in 2009. Measurement of urine excretion of albumin, IgG, and protein HC were performed in the early morning of spot urine samples collected at the time of the diagnostic renal biopsy. Patients were stratified according to urine protein concentrations and the progression rate to end-stage renal disease (ESRD) calculated using Kaplan-Meier survival analysis. ESRD was defined as the start of renal replacement therapy. RESULTS: During the study follow-up time of 1429 person-years; 26 (13.8%) patients reached ESRD. The overall mean kidney survival time of studied patients with serum creatinine less than 150 were 13.4 years. The incidence rate of ESRD was ∼18 per 1000 person-years. Stratified analysis identified urinary excretion of IgG, but not albuminuria, as predictor of ESRD. The progression rate to ESRD was 36 per 1000 person-years in patients with urine IgG concentration exceeding 5 mg/mmol urine creatinine, compared to a progression rate of 6/1000 person-years for patients with lower levels of urine IgG. CONCLUSION: The findings of the study suggest that at early stages, the level of IgG-uria is useful to be used in risk stratification of patients with proteinuric glomerular diseases.

COVID-19 epidemic in Libya.

The first case of COVID-19 was identified in Libya on 24/3/2020, and about 2 months later, the number of reported COVID-19 cases started to increase notably. The outbreak was first prominent in the southern region (Sabha) and then spread to the western and eastern parts of Libya. By 24/12/2020, the reported total number of deaths from COVID-19 reached 1415. There seems to be no published data on the size of the epidemic in Libya. Here, we estimated the number of Libyans exposed to COVID-19 by using a COVID-19 mortality adjusted mathematical model for the spread of infectious diseases. We estimated that 14-20% of the Libyan population have been exposed to the COVID-19 pandemic. Thus, the risk of spread of COVID-19 infections during the coming months is high, and a considerable number of Libyans, particularly the elderly and people with chronic diseases, should be protected against COVID-19 infection. This is particularly urgent in the light of unofficial reports that the relevant healthcare facilities are under extreme stress.

Development and validation of GFR-estimating equations using diabetes, transplant and weight.

BACKGROUND: We have reported a new equation (CKD-EPI equation) that reduces bias and improves accuracy for GFR estimation compared to the MDRD study equation while using the same four basic predictor variables: creatinine, age, sex and race. Here, we describe the development and validation of this equation as well as other equations that incorporate diabetes, transplant and weight as additional predictor variables. METHODS: Linear regression was used to relate log-measured GFR (mGFR) to sex, race, diabetes, transplant, weight, various transformations of creatinine and age with and without interactions. Equations were developed in a pooled database of 10 studies [2/3 (N = 5504) for development and 1/3 (N = 2750) for internal validation], and final model selection occurred in 16 additional studies [external validation (N = 3896)]. RESULTS: The mean mGFR was 68, 67 and 68 ml/min/ 1.73 m(2) in the development, internal validation and external validation datasets, respectively. In external validation, an equation that included a linear age term and spline terms in creatinine to account for a reduction in the magnitude of the slope at low serum creatinine values exhibited the best performance (bias = 2.5, RMSE = 0.250) among models using the four basic predictor variables. Addition of terms for diabetes and transplant did not improve performance. Equations with weight showed a small improvement in the subgroup with BMI <20 kg/m(2). CONCLUSIONS: The CKD-EPI equation, based on creatinine, age, sex and race, has been validated and is more accurate than the MDRD study equation. The addition of weight, diabetes and transplant does not significantly improve equation performance.

Increased urine IgM excretion predicts cardiovascular events in patients with type 1 diabetes nephropathy.

BACKGROUND: Diabetic nephropathy, a major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality. An increased urinary albumin excretion due dysfunction of the glomerular barrier is an early sign of diabetic nephropathy. An increased urinary excretion of higher molecular weight proteins such as IgM appears with progression of glomerular injury. We aim here to study the prognostic significance of urine IgM excretion in patients with type 1 diabetes mellitus (type 1 diabetic nephropathy). METHODS: This is an observational study of 139 patients with type 1 diabetes mellitus (79 males and 60 females) under routine care at the diabetic outpatient clinic at the Lund University Hospital. The median follow-up time was 18 years (1 to 22) years. Urine albumin and urine IgM concentration were measured at time of recruitment. RESULTS: Overall 32 (14 male and 18 female) patients died in a cardiovascular event and 20 (11 male and 9 female) patients reached end-stage renal disease. Univariate analysis indicated that patient survival and renal survival were inversely associated with urine albumin excretion (RR = 2.9 and 5.8, respectively) and urine IgM excretion (RR = 4.6 and 5.7, respectively). Stratified analysis demonstrated that in patients with different degrees of albuminuria, the cardiovascular mortality rate and the incidence of end-stage renal disease was approximately three times higher in patients with increased urine IgM excretion. CONCLUSION: An increase in urinary IgM excretion in patients with type 1 diabetes is associated with an increased risk for cardiovascular mortality and renal failure, regardless of the degree of albuminuria.

Arab nations lagging behind other Middle Eastern countries in biomedical research: a comparative study.

BACKGROUND: Analysis of biomedical research and publications in a country or group of countries is used to monitor research progress and trends. This study aims to assess the performance of biomedical research in the Arab world during 2001-2005 and to compare it with other Middle Eastern non-Arab countries. METHODS: PubMed and Science Citation Index Expanded (SCI-expanded) were searched systematically for the original biomedical research publications and their citation frequencies of 16 Arab nations and three non-Arab Middle Eastern countries (Iran, Israel and Turkey), all of which are classified as middle or high income countries. RESULTS: The 16 Arab countries together have 5775 and 14,374 original research articles listed by PubMed and SCI-expanded, respectively, significantly less (p < 0.001) than the other three Middle Eastern countries (25,643 and 49,110). The Arab countries also scored less when the data were normalized to population, gross domestic product (GDP), and GDP/capita. The publications from the Arab countries also have a significantly lower (p < 0.001) citation frequency. CONCLUSION: The Arab world is producing fewer biomedical publications of lower quality than other Middle Eastern countries. Studies are needed to clarify the causes and to propose strategies to improve the biomedical research status in Arab countries.

Monocyte chemoattractant protein 1 is a prognostic marker in ANCA-associated small vessel vasculitis.

BACKGROUND: The (anti neutrophil cytoplasmatic autoantibody ANCA), associated small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders, involving various organs, such as the kidneys. (Monocyte chemoattractant protein 1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and recent studies have pointed out MCP-1 as a promising marker of renal inflammation. Here we measure urinary cytokine levels in different phases of disease, exploring the possible prognostic value of MCP-1, together with (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). METHODS: MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits, whereas IgM in the urine was measured by an in-house ELISA. RESULTS: The MCP-1 levels in urine were significantly higher in patients in stable phase of the disease, compared with healthy controls. Patients in stable phase, with subsequent adverse events; had significantly higher MCP-1 values than patients who did not. MCP-1 and IgM both tended to be higher in patients relapsing within three months, an observation, however, not reaching statistical significance. Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated with disease outcome. CONCLUSIONS: Patients with ASVV have raised cytokine levels in the urine compared to healthy controls, even during remission. Raised MCP-1 levels are associated with poor prognosis and possibly also with relapse tendency. The association with poor prognosis was stronger for U-MCP-1 than for conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have promising potential as a prognostic marker in ASVV.